title: Different effects of human neutrophil elastase on platelet glycoproteins IIb and IIIa of resting and stimulated platelets.
abstract: The effect of human neutrophil elastase (HNE) on the structure and receptor activity of platelet glycoprotein IIb/IIIa complex was studied. Resting platelets, which bound only traces of 125I-fibrinogen in the absence of ADP, were found to be barely susceptible to HNE. As shown by immunoblotting experiments, treatment of such platelets with HNE (14 micrograms/ml) did not provoke a detectable cleavage of GPIIb but resulted in a partial digestion of GPIIIa and appearance of 110 kDa fragment. Such proteolytic modification of the GPIIb/IIIa complex was accompanied by a slight increase in the binding of fibrinogen to blood platelets in the absence of ADP. Treatment of partially activated platelets (spontaneous activation during washing procedure) with HNE caused a progressive loss of GPIIb and degradation of GPIIIa to 110 kDa and 60 kDa fragments. These spontaneously stimulated platelets had initially a high number of fibrinogen binding sites exposed, corresponding to approximately 50% of receptor capacity observed in platelets activated by the optimal concentration of ADP. Digestion of GPIIb/IIIa by HNE of such platelets markedly increased the exposure of fibrinogen receptors. Thus, the stimulation of platelets increases significantly the susceptibility of the GPIIb/IIIa complex to proteolysis by HNE. However, such modification of the GPIIb/IIIa does not destroy its function as a receptor for fibrinogen either on the resting or activated platelets.
authors.affiliation: Laboratory of Blood Coagulation and Haemostasis, Institute of Haematology, Warsaw, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Bykowska
authors.forename: Z
authors.initials: Z
authors.lastname: Pawlowska
authors.forename: C
authors.initials: C
authors.lastname: Cierniewski
authors.forename: S
authors.initials: S
authors.lastname: Lopaciuk
authors.forename: M
authors.initials: M
authors.lastname: Kopeć
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007457:Iodine Radioisotopes; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000097:blood*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*
chemical_list: D007457:Iodine Radioisotopes; D010980:Platelet Membrane Glycoproteins; D010196:Pancreatic Elastase